The mammalian immune system is very complex; and disorder in its regulation may affect other organs in a number of ways. Lymphocytes and macrophages may directly attack cells of the body. Various metabolic products of these cells may be deleterious to tissue. Antibodies against autoantigens can accumulate in the kidneys and joints.
Several neurological disorders are thought to have an autoimmune component. In animal models for multiple sclerosis, T lymphocytes reactive with myelin basic protein can trigger disease symptoms. HIV infection is well known to have various neuropathies associated with it, where the degeneration of neural cells and demyelination may be directly caused by the action of cells in the immune system.
HIV infected patients with neurological disorders have increased neopterin levels in cerebrospinal fluid, possibly as a result of .gamma.-interferon leading to increased synthesis of neopterin in monocytes and macrophages. Excess production of dihydroneopterin may lead to folate deficiency causing demyelination in the brain. Indolamine-2,3 -dioxygenase activity is also increased by exposure to .gamma.-interferon, leading to increased conversion of tryptophan to various metabolites, including quinolonic acid, which is neurotoxic.
Neural cells are sensitive-to deficiencies in methyl group metabolism. At the present time there is not a definitive answer as to why this happens, although a number of theories have been postulated. The major pathway for methylation in humans is through S-adenosylmethionine (SAM). The immediate precursor to SAM is methionine, which is produced by a pathway where 5-methyltetrahydrofolate transfers a methyl group to cobalamin, forming methylcobalamin, which in turn methylates homocysteine to form methionine. The cycling of homocysteine to methionine is required to maintain methylation homeostasis. It is possible that myelin basic protein is particularly unstable when there is a methionine deficiency. SAM is also required for the biosynthesis of phospholipids, which are required for neural function.
In the treatment of neurological disorders with methyl-donor compounds to restore normal methyl-group metabolism, it is beneficial to the host to use compounds which can positively affect the underlying immune disorder.